New β-Lactamase Inhibitors in the Clinic

Infect Dis Clin North Am. 2016 Jun;30(2):441-464. doi: 10.1016/j.idc.2016.02.007.

Abstract

Given the serious medical burden of β-lactamases, many approaches are being used identify candidate agents for β-lactamase inhibition. Here, we review two β-lactam-β-lactamase inhibitor (BL-BLI) combinations, ceftolozane-tazobactam and ceftazidime-avibactam that recently entered the clinic. In addition, we focus on BL-BLI combinations in preclinical development that have demonstrated activity in clinical isolates via susceptibility testing and/or in in vivo models of infection. We highlight only the BLIs that are able to reduce the Clinical Laboratory Standards Institute (CLSI) breakpoints for the BL partner into the susceptible range. Our analysis includes the primary literature, meeting abstracts, as well as the patent literature.

Keywords: Boronic acids; Carbapenems; Diazabicyclooctanones; Inhibitor; Metallo-beta-lactamases; Monobactams; Sulfones; β-Lactamases.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents*
  • Azabicyclo Compounds
  • Boronic Acids
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / enzymology
  • Gram-Negative Bacteria / pathogenicity
  • Gram-Negative Bacterial Infections* / drug therapy
  • Gram-Negative Bacterial Infections* / microbiology
  • Humans
  • Sulfones
  • beta-Lactam Resistance
  • beta-Lactamase Inhibitors*

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Boronic Acids
  • Sulfones
  • beta-Lactamase Inhibitors